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• W2772977319 abstract "// Claudia Paret 1, 14, * , Alexandra Russo 1, 14, * , Henrike Otto 1, 14 , Arnulf Mayer 2 , Sebastian Zahnreich 2 , Wolfgang Wagner 3 , David Samuel 4 , David Scharnhorst 5 , David A. Solomon 6 , Girish Dhall 7 , Kenneth Wong 8 , Hannah Bender 1 , Francesca Alt 1, 14 , Arthur Wingerter 1, 14 , Marie A. Neu 1, 14 , Olaf Beck 1, 14 , Dirk Prawitt 9 , Stefan Eder 1, 14 , Nicole Henninger 1, 14 , Khalifa El Malki 1, 14 , Nadine Lehmann 1, 14 , Nora Backes 1, 14 , Lea Roth 1, 14 , Larissa Seidmann 10 , Clemens Sommer 11 , Marc A. Brockmann 12 , Gundula Staatz 13 , Heinz Schmidberger 2 and Jörg Faber 1, 14 1 Section of Pediatric Oncology, Children's Hospital, University Medical Center of The Johannes Gutenberg University Mainz, Mainz, Germany 2 Department of Radiation Oncology and Radiation Therapy, University Medical Center of The Johannes Gutenberg University Mainz, Mainz, Germany 3 Section of Pediatric Neurosurgery, Department of Neurosurgery, University Medical Center of The Johannes Gutenberg University Mainz, Mainz, Germany 4 Department of Oncology, Valley Children’s Hospital, Madera, California, USA 5 Department of Pathology, Valley Children’s Hospital, Madera, California, USA 6 Division of Neuropathology, University of California, San Francisco, California, USA 7 Division of Hematology, Oncology and Blood & Marrow Transplantation, Children’s Hospital Los Angeles, Los Angeles, California, USA 8 Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California, USA 9 Center for Pediatrics and Adolescent Medicine, Children's Hospital, University Medical Center of The Johannes Gutenberg University Mainz, Mainz, Germany 10 Institute of Pathology, University Medical Center of The Johannes Gutenberg University Mainz, Mainz, Germany 11 Division of Neuropathology, University Medical Center of The Johannes Gutenberg University Mainz, Mainz, Germany 12 Department of Neuroradiology, University Medical Center of The Johannes Gutenberg University Mainz, Mainz, Germany 13 Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, University Medical Center of The Johannes Gutenberg University Mainz, Mainz, Germany 14 University Cancer Center of The Johannes Gutenberg University, Mainz, Germany * These authors have contributed equally to the work Correspondence to: Claudia Paret, email: claudia.paret@unimedizin-mainz.de Keywords: ATO; HGNET-BCOR; radiation; liquid biopsy; targeted therapy Received: August 09, 2017      Accepted: November 16, 2017      Published: December 11, 2017 ABSTRACT High-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a rare, highly malignant tumor. At the time of this publication, no standard protocol exists to treat this tumor entity. In this work, we tested the responsiveness of the primary culture PhKh1 derived from tumor tissue from a pediatric HGNET-BCOR patient (P1) to inhibitors of the Sonic hedgehog pathway combined with radiation. The SMO inhibitors vismodegib and itraconazole had low effect on the proliferation of the PhKh1 cells. However, the GLI inhibitor arsenic trioxide reduced the expression of GLI target genes in the PhKh1 cells and in combination with radiotherapy significantly decreased their clonogenic potential. PhKh1 cells resistant to arsenic trioxide were characterized by the overexpression of molecular chaperones. We combined arsenic trioxide and radiation in the relapse therapy protocol of P1, achieving complete remission after seven weeks. Clinical remission lasted for six months, when P1 developed systemic metastases. Meanwhile, an increase in the concentration of circulating tumor DNA carrying a BCOR internal tandem duplication was observed. Molecular characterization of a second patient (P2) was also performed. In P2, we detected a larger tandem duplication and greater activation of the Sonic hedgehog pathway than in P1. These findings suggest that combining arsenic trioxide with radiotherapy may represent a new therapeutic approach. Moreover, peripheral blood analysis for circulating tumor DNA could help in the early detection of systemic metastases." @default.
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• W2772977319 date "2017-12-11" @default.
• W2772977319 modified "2023-10-13" @default.
• W2772977319 title "Personalized therapy: CNS HGNET-BCOR responsiveness to arsenic trioxide combined with radiotherapy" @default.
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• W2772977319 doi "https://doi.org/10.18632/oncotarget.23174" @default.
• W2772977319 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5768397" @default.
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• W2772977319 hasPublicationYear "2017" @default.
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